Selective modification of sucralose presents a major synthetic challenge because of the multiplicity of reactive —OH groups and the acid lability of the glycosidic linkage. When the target of interest is sucralose (4,1′,6′-trichloro-4,1′,6′-trideoxygalactosuccrose: in the process of making the compound, the stereo configuration at the 4 position is reversed; therefore, sucralose is a galacto-sucrose), the difficulty is compounded by a need to chlorinate the less reactive 4- and 1′-positions, while leaving intact the more reactive 6-position.
A number of different strategies for the preparation of sucralose have been developed to preblock the 6-position, usually by forming a sucralose-6-acylate such as sucralose-6-acetate and removing the blocking moiety as by hydrolysis after chlorination to produce sucralose. U.S. Pat. Nos. 4,950,746; 5,023,329; 5,034,551; 5,470,969; 4,362,869; 4,826,962; 5,470,969; 5,530,106; and 4,980,473, which are expressly incorporated by reference herein, relate to such strategies.
Prior to the isolation of pure sucralose, the sucralose-6-acylate is desterified by hydrolysis. In one approach, the ester groups are converted back to free hydroxyl groups by alkaline hydrolysis. After the hydrolysis, the feed mixture is adjusted to approximately neutral pH, and the sucralose is subsequently purified from the feed mixture by any one of several acceptable processes. See, e.g., the U.S. patent applications entitled “Extractive Methods for Purifying Sucralose” and “Process for Improving Sucralose Purity and Yield,” filed 8 Mar. 2002, and expressly incorporated by reference herein. The de-esterification reaction may be carried in an organic system employing a material such as sodium methoxide that produces a transesterification reaction. In this case, the acid moiety forming the sucralose ester is converted to the methyl ester of the acid, whereby the methyl ester may be removed by distillation, driving the reaction to completion. Alternatively, the de-esterification reaction may be carried out in water under alkaline conditions, resulting in a base-mediated conversion of ester to sucralose and the salt of the acid that was used to form the ester. The latter use of an aqueous hydrolysis is desirable because it avoids the use of expensive solvents that must be removed during the later purification.
However, one problem with the latter sucralose purification strategy is that sucralose in the de-esterified form is unstable under intensely alkaline conditions and may be converted to undesirable compounds. For example, the anhydro compounds are undesirable because they decrease the overall reaction yield, and they affect the sweetness properties of sucralose. Hence, such undesirable compounds may also affect the duration of the extraction process. Moreover, high levels of such material greatly increase the difficulty of these purification steps.
The present invention provides processes whereby the acyl-sucralose compound is deacylated directly to produce an aqueous solution of sucralose including salts and other compounds, from which sucralose is recovered and preferably then purified by counter-current extraction, crystallization, or a combination of such techniques.
Accordingly, the present invention provides a sucralose purification process that produces sucralose compositions of enhanced purity and also minimizes the overall loss of sucralose during the purification process prior to any specific extraction, while reducing the formation of undesirable compounds such as anhydro sucralose.